Maintenance of tissue homeostasis is dependent on the communication between stem cells and supporting cells in the same niche. Regulatory T cells (T_reg cells) are emerging as a critical component of the stem-cell niche for supporting their differentiation. How T_reg cells sense dynamic signals in this microenvironment and communicate with stem cells is mostly unknown. In the present study, by using hair follicles (HFs) to study T_reg cell–stem cell crosstalk, we show an unrecognized function of the steroid hormone glucocorticoid in instructing skin-resident T_reg cells to facilitate HF stem-cell (HFSC) activation and HF regeneration. Ablation of the glucocorticoid receptor (GR) in T_reg cells blocks hair regeneration without affecting immune homeostasis. Mechanistically, GR and Foxp3 cooperate in T_reg cells to induce transforming growth factor β3 (TGF-β3), which activates Smad2/3 in HFSCs and facilitates HFSC proliferation. The present study identifies crosstalk between T_reg cells and HFSCs mediated by the GR–TGF-β3 axis, highlighting a possible means of manipulating T_reg cells to support tissue regeneration.

组织稳态的维持取决于同一生态位中干细胞和支持细胞之间的交流。调节性 T 细胞（T _reg细胞）正在成为支持其分化的干细胞生态位的重要组成部分。T _reg细胞如何感知这种微环境中的动态信号并与干细胞进行交流，这在很大程度上是未知的。在本研究中，通过使用毛囊 (HF) 研究 T _reg细胞-干细胞串扰，我们展示了类固醇激素糖皮质激素在指导皮肤驻留 T _reg细胞促进 HF 干细胞 (HFSC) 激活方面未被认识的功能和高频再生。_{T reg}中糖皮质激素受体 (GR) 的消融细胞阻止毛发再生而不影响免疫稳态。从机制上讲，GR 和 Foxp3 在 T _reg细胞中协同诱导转化生长因子 β3 (TGF-β3)，后者激活 HFSC 中的 Smad2/3 并促进 HFSC 增殖。本研究确定了由 GR-TGF-β3 轴介导的 T _reg细胞和 HFSC 之间的串扰，强调了一种可能的操纵 T _reg细胞以支持组织再生的方法。